Germfree and conventional Lobund Wistar (L-W) and ACI rats will be examined and used for studies on spontaneous and induced prostate cancer. Rats of the two susceptible strains will be subjected to treatments with androgens and with estrogens to determine if pathogenesis of disease can be promoted in them. Four lines of transplantable tumor cells (PA-I, II, III, IV), derived from L-W rats, will be examined in relation to growth of primary tumor and the metastatic spread thereof through defined routes to predetermined target organs. PA-I, III and IV metastasize only through lymphatic channels to the lungs, while PA-II cells spread through lymphatics and blood to multiple visceral target organs, including bone marrow. The phenomenon of metastasis will be examined to determine if it is a unique manifestation of (a) The tumor cell, (b) Host resistance of submission, or (c) A combination of both. This will be related to cell-mediated activities (macrophages, lymphocytes), to modulators (interferons I and II, VLDL), and/or to enzymes (glycoprotein transferases, plasminogen activators, collagenases, elastase, and other proteases, and prostaglandins). The effect(s) of whole-body irradiation, of anti-macrophage agents and other immunosuppressive drugs will be determined in order to further characterize the phenomenon of metastasis. The colony-inhibition technique will serve as a preliminary in vitro screening procedure to detect and assess putative anti-tumor agents and the results will then be applied to tumor-bearing rats. The in vivo assays will be based on numbers of tumor foci in the lungs (PA-I, III, IV), and on WBC counts, weights of liver, spleen, lymph nodes (PA-II) to determine if modulation of the anticipated pattern of growth and spread of the tumor has occurred, and the possible reasons for that change. The model systems involve in vivo and in vivo procedures with the same tumor lines, and the cells metastasize spontaneously from all sites into which they are implanted to specific target organs.